Dataset Information

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

ABSTRACT:

Backgrounds

Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated.

Methods

Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay.

Results

Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice.

Conclusions

These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.

SUBMITTER: Alenazy MF

PROVIDER: S-EPMC9447931 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

Alenazy Maha Fahad MF Sharif-Askari Fatemeh Saheb FS El-Wetidy Mohammed S MS Sharif-Askari Narjes Saheb NS Hachim Ibrahim Yaseen IY Temsah Mohammad-Hani MH Saddik Basema B Al-Kufaidy Roua R Omair Maha A MA Alshawakir Yasser A YA Fathaddin Amany Adulgadel AA Hannawi Suad S Hamid Qutayba Q Omair Mohammed A MA Al-Muhsen Saleh S Halwani Rabih R

PloS one 20220906 9

<h4>Backgrounds</h4>Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated.<h4>Methods</h4>Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive c ...[more]

PMID: 36067164

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Project description:Allergy is a major public health concern, the main treatment for which is symptomatic relief with anti-inflammatory drugs. A key clinical challenge is to induce specific tolerance in order to control allergen-specific memory B and T cells, and specifically block effector cell responses. Our lab recently developed antigen-specific regulatory T-cell (Treg) therapies as a treatment for adverse responses. Recently, we created a chimeric antigen receptor (CAR) approach in which we engineered a target protein antigen, ovalbumin (OVA), linked with the transmembrane and signal transduction domains, CD28-CD3ζ to directly target B cells and sensitized mast cells in an allergy model. We named this receptor "BAR" for B-cell Antibody Receptor. Murine or human Tregs, transduced with a BAR containing OVA or control Tregs expressing an unrelated antigen, were successfully expanded in vitro and tested in the murine OVA-alum allergy model with measurable titers of anti-OVA IgE. Because BAR Tregs express the target antigen and could interact with specific IgE on sensitized mast cells, we first demonstrated that intravenously injected OVA-BAR Tregs did not directly lead to a drop in temperature or release of mediators in plasma indicative of anaphylaxis. Forty-eight hours later, mice were challenged intraperitoneally with 200 μg OVA to induce an anaphylactic reaction, and temperature immediately measured for 30 min. We found that OVA-BAR Tregs protected mice from hypothermia, whereas mice given control BARs (expressing an unrelated antigen) or PBS showed substantial temperature drops indicative of anaphylaxis when systemically challenged with OVA. Importantly, this effect was also demonstrated in a passive anaphylaxis model in which mice that received anti-OVA IgE antibody were protected from hypothermia when treated with OVA-BAR Tregs prior to systemic OVA challenge. These results provide proof of principle that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE-sensitized to an allergen.

Dataset Information

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

Backgrounds

Methods

Results

Conclusions

Publications

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

Similar Datasets

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